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Biomedical subjects

I Fuse

Publications and source records attributed to I Fuse.

At least 37 records · Page 2Linked to original sources
PubMed1998

Myocardial CD36 expression and fatty acid accumulation in patients with type I and II CD36 deficiency.

Long-chain fatty acids (LCFA) are one of the major cardiac energy substrates, so understanding LCFA metabolism may help in elucidating the mechanisms of various heart diseases. CD36 is a multifunctional membrane glycoprotein that acts not only as a receptor for thrombospondin, collagen and oxidized low density lipoprotein but also as a receptor for LCFA. We investigated the relationship between CD36 expression in myocardial capillary endothelial cells and myocardial LCFA uptake in patients with CD36 deficiency. We analyzed CD36 expression in blood cells from 250 patients with heart diseases by means of a flow cytometer. In 218 patients, myocardial LCFA scintigraphy was performed with 123I-beta-methyl-p-iodophenyl pentadecanoic acid (BMIPP). In 5 patients, myocardial capillary endothelial cells were examined immunohistochemically for CD36 expression. Eleven patients (4%) showed signs of type I CD36 deficiency (neither platelets nor monocytes expressed CD36). Twenty patients (8%) had type II CD36 deficiency (monocytes expressed CD36 but platelets did not). In all 11 patients with type I CD36 deficiency, no BMIPP accumulation was observed in the heart, but in 13 patients with type II CD36 deficiency, BMIPP accumulation in the heart was focally reduced, but there were no patients without BMIPP accumulation in the heart. Although the myocardial capillary endothelial cells from two CD36-positive patients expressed CD36, those from two patients with type I CD36 deficiency did not. In a patient with type II CD36 deficiency, some capillary endothelial cells displayed patchy CD36 expression. CD36 deficiency was documented in 31 (12%) patients with heart diseases. Because CD36 was not expressed in the myocardial capillary endothelial cells in patients with type I CD36 deficiency, type I CD36 deficiency is closely related to lack of myocardial LCFA accumulation and metabolism in the myocardium.

Adult↗
PubMed1998

Overproduction of antiplatelet antibody against glycoprotein IIb after splenectomy in a patient with Evans syndrome resulting in acquired thrombasthenia.

We treated a 33-year-old female with Evans syndrome. She received high dose gamma globulin, prednisolone, and azathioprine, and her platelet count transiently increased. After splenectomy, the platelet count markedly increased. However, the bleeding tendency worsened and the bleeding time was prolonged. A platelet defect, characteristic of thrombasthenia, was found. Antigen-captured ELISA and Western blotting revealed that the patient's serum had an IgG autoantibody against platelet membrane glycoprotein IIb and the patient's plasma inhibited normal platelet aggregation. These findings suggest that overproduction of the antiplatelet antibody is triggered by platelet recovery due to splenectomy and affects platelet function resulting in acquired thrombasthenia.

Adenine Nucleotides↗
PubMed1998

Hypertrophic cardiomyopathy with type I CD36 deficiency.

CD36 is a multifunctional membrane-type receptor glycoprotein that reacts with oxidized low-density lipoprotein and long-chain fatty acid (LCFA). A patient presented with hereditary hypertrophic cardiomyopathy (HCM) and type I CD36 deficiency (neither platelets nor monocytes expressed CD36) but showed no myocardial LCFA accumulation. CD36 was expressed in the capillary endothelial cells of the cardiac muscle of a control subject, while the patient's myocardial capillary endothelial cells were completely CD36-negative. These results suggest that type I CD36 deficiency is closely related to hereditary HCM and lack of myocardial LCFA accumulation.

CD36 Antigens↗
PubMed1997

Acquired immune thrombocytopenia caused by IgG antiglycoprotein Ib antibody in a patient with Hodgkin's disease.

We studied a patient with thrombocytopenia associated with Hodgkin's disease (HD). The megakaryocyte number in the bone marrow and the level of platelet-associated IgG were both increased in the patient. Intravenous gamma-globulin therapy and chemotherapy for HD dramatically normalized the platelet count, suggesting that antibody produced by lymphoma cells is likely to account for the thrombocytopenia. Antigen-captured ELISA and Western blotting showed that the patient's serum had an IgG autoantibody against platelet membrane glycoprotein Ib. The patient's plasma had no inhibitory effect on normal platelet aggregation induced by ristocetin. These findings suggest that the autoantibody found in the patient had a pathogenetic role in the thrombocytopenia, but not in platelet dysfunction.

Adolescent↗
PubMed1996

Vascular thromboxane formation in hemostasis mechanism: correlation between bleeding time and vascular TXB2 in a patient with congenital platelet cyclo-oxygenase deficiency.

We encountered a patient with congenital platelet cyclo-oxygenase deficiency with normal ability to synthesize vascular prostaglandin I2 (PGI2) and thromboxane A2 (TXA2). The patient's peripheral blood monocytes did not show cyclo-oxygenase (COX) activity, but cultured bone marrow fibroblasts showed COX activity. To determine the mechanism of primary hemostasis in this patient, we examined the effect of oral administration of aspirin (1 g) on bleeding time and thromboxane B2 (TXB2), 6-keto prostaglandin F1 alpha (6-keto-PGF1 alpha) production in the blood emerging from the incision in this patient. The bleeding time was markedly prolonged by the administration of aspirin, and this prolongation was associated with the inhibition of TXB2 in the effluent blood, which seemed to be derived from the vessel wall. These findings suggest that vascular TXA2 production plays an important role in the maintenance of hemostasis.

6-Ketoprostaglandin F1 alpha↗
PubMed1996

Disorders of platelet function.

Qualitative platelet disorders are described and reviewed above. The acquired platelet function defects are very common, and sometimes result in hemorrhage, especially in association with trauma or surgery. However, the specific biochemical defect is absent, and no characterized platelet abnormalities have been recognized. On the other hand, the hereditary qualitative platelet defects are rare, but the platelet abnormalities are characteristic. The study of these patients had led to an increased understanding of the normal primary hemostatic mechanism. Recently, the molecular basis analysis of the platelet defects has been developed. This will help us understand the molecular events involved in platelet adhesion and aggregation.

Antigens, Human Platelet↗
PubMed1996

Abnormal function of platelet G proteins in long QT syndrome.

Several hypotheses have been proposed for the pathophysiology of the congenital long QT syndrome, however, the underlying mechanism has not yet been elucidated. This study evaluated G protein function in patients with congenital long QT syndrome (LQTS) and compared it with that of normal subjects. Platelet-rich plasma was collected and the cyclic AMP (cAMP) level of platelets was measured in three conditions utilizing radioimmunoassay: the basal state (Basal cAMP), after stimulation by PGE1 (PGE1-cAMP), and after stimulation by PGE1 followed by inhibition by adrenaline (Adr-cAMP), and the results were compared between 7 LQTS patients and 10 healthy volunteers (control). Gs function was defined as (PGE1-cAMP)/(Basal cAMP) and Gi function as ¿(PGE1-cAMP)-(Adr-cAMP)¿/(PGE1-cAMP). Basal cAMP was lower in patients than in the controls: 2.9 +/- 0.6 pmol/ 10(8) cells vs. 4.2 +/- 0.7 pmol/10(8) cells (p < 0.05). The increase in cAMP after PGE1 was similar in the two groups but the peak was lower in the patients: 16.8 +/- 6.2 pmol/10(8) cells vs. 24.8 +/- 7.4 pmol/10(8) cells (PGE1-cAMP). After addition of adrenaline, cAMP decreased to 14.2 +/- 5.8 pmol/10(8) cells vs. 16.2 +/- 7.6 pmol/10(8) cells and the change was significantly smaller in the patients than in the controls: 0.17 +/- 0.12 vs. 0.38 +/- 0.16 (p < 0.05). Basal cAMP was weakly correlated with sinus cycle length (r = -0.48, p > 0.3) and QTc was correlated with Gs function (r = 0.52, p > 0.3) but not with Gi function. Patients with associated Torsade de Pointes had a significantly lower Gi function compared to those without (p < 0.05). In LQTS patients, G protein function was abnormal and the abnormality was associated with clinical characteristics of long QT syndrome. The relationship between the abnormal G protein function and the regulation of the repolarization of the ventricular myocardium needs to be studied further.

Adolescent↗
PubMed1996

Severe cryoglobulinemia in a patient with asymptomatic hepatitis C virus infection.

A patient with severe type II cryoglobulinemia after ten years of asymptomatic hepatitis C virus (HCV) infection is reported. Laboratory data showed hypergammaglobulinemia with polyclonal IgG and monoclonal IgM, blood hyperviscosity, high level of cryocrit (60%), HCV viremia, and normal levels of serum transaminases. Due to cold exposure, acrocyanosis and cardiac ischemic attack occurred; he recovered after being artificially warmed. Administration of prednisolone and natural interferon-alpha for three months resulted in significant decreases in the levels of serum IgM and cryocrit.

Cryoglobulinemia↗
PubMed1996

Pathogenetic analysis of five cases with a platelet disorder characterized by the absence of thromboxane A2 (TXA2)-induced platelet aggregation in spite of normal TXA2 binding activity.

Five patients with mild bleeding tendencies characterized by defective thromboxane A2 (TXA2)-induced platelet aggregation are reported. The platelets of all the patients had the ability to bind exogenous TXA2. Bleeding time was markedly prolonged in one patient. In three of the five patients, synthetic TXA2 mimetic (STA2)-induced platelet responses, including IP3 formation, Ca2+ mobilization, phosphatidic acid formation and GTPase activities were selectively defective, suggesting impaired coupling between the TXA2 receptor and phospholipase C activation. However, in the remaining two patients, these responses were all within normal limits. This suggests that the defective site of this type of platelet disorder is heterogenous and that signaling mechanisms other than the TXA2 receptor-phospholipase C pathway are also involved in TXA2-induced platelet aggregation.

Adult↗
PubMed1995

[Essential thrombocythemia in transformation to smouldering megakaryoblastic leukemia with myelofibrosis].

Leukemic transformation in essential thrombocythemia (ET) is rare. We describe a patient with ET which transformed to megakaryoblastic leukemia with myelofibrosis after treatment with melphalan for 8 years. His course after transformation smouldered for 20 months without antileukemic chemotherapy. A 61-year-old man was referred by a local doctor to Niigata University Hospital due to nasal bleeding in June 1984. Complete blood count (CBC) was as follows; hemoglobin 12.4 g/dl, platelets 268.8 x 10(4)/microliters, and white blood cells 11,900/microliters, with differentials of 39% PMN, 1% basophils, 2% eosinophils, 4% monocytes, and 13% lymphocytes. Bone marrow examination revealed hyperplasia of megakaryocytes without increase of reticulin fibers. Neutrophil alkaline phosphatase activity and karyotype of marrow cells were normal. ET was diagnosed. He was followed up by local doctor. The platelet count was controlled at a level of approximately 40 x 10(4)/microliters with melphalan for eight years. In January 1992 he developed pain in his lower extremities. He was admitted to our hospital on May 29, 1992. CBC was as follows; hemoglobin 8.9 g/dl, platelets 14.3 x 10(4)/microliters, and white blood cells 3,500/microliters, with differentials of 25% PMN, 5% monocytes, 28% lymphocytes, and 24% blasts. Bone marrow aspiration was unsuccessful and bone marrow biopsy revealed increases in fibroblasts and collagen fibers. Circulating blasts were positive for CD4, CD7, CD25, CD13, CD33, CD34, and HLA-DR and partly positive for CD41 and CD36. In ultrastructural cytochemistry blasts were positive for platelet peroxidase but negative for myeloperoxidase. Cytogenetic study revealed 46, XY, +der (1) t(1:7) (p11;q11) in all of five metaphases. He was diagnosed with megakaryoblastic leukemia accompanied by myelofibrosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1994

Arg60 to Leu mutation of the human thromboxane A2 receptor in a dominantly inherited bleeding disorder.

Recent advances in molecular genetics have revealed the mechanisms underlying a variety of inherited human disorders. Among them, mutations in G protein-coupled receptors have clearly demonstrated two types of abnormalities, namely loss of function and constitutive activation of the receptors. Thromboxane A2 (TXA2) receptor is a member of the family of G protein-coupled receptors and performs an essential role in hemostasis by interacting with TXA2 to induce platelet aggregation. Here we identify a single amino acid substitution (Arg60-->Leu) in the first cytoplasmic loop of the TXA2 receptor in a dominantly inherited bleeding disorder characterized by defective platelet response to TXA2. This mutation was found exclusively in affected members of two unrelated families with the disorder. The mutant receptor expressed in Chinese hamster ovary cells showed decreased agonist-induced second messenger formation despite its normal ligand binding affinities. These results suggest that the Arg60 to Leu mutation is responsible for the disorder. Moreover, dominant inheritance of the disorder suggests the possibility that the mutation produces a dominant negative TXA2 receptor.

Amino Acid Sequence↗
PubMed1993

Defective signal transduction induced by thromboxane A2 in a patient with a mild bleeding disorder: impaired phospholipase C activation despite normal phospholipase A2 activation.

A patient with a mild bleeding disorder whose platelets responded defectively to thromboxane A2 (TXA2) was identified, and the mechanism of this dysfunction was analyzed. The platelets were defective in shape change, aggregation, and release reaction in response to synthetic TXA2 mimetic (STA2). When the platelet TXA2 receptor was examined with both a 125I-labeled derivative of a TXA2 receptor antagonist ([125I]-PTAOH) and [3H]-labeled TXA2 agonist ([3H]U-46619), the equilibrium dissociation rate constants (kd) and the maximal concentrations of binding sites (Bmax) of the platelets to both ligands were within normal ranges, suggesting that the binding capacity of their TXA2 receptor was normal. STA2 could not induce IP3 formation and intracellular Ca2+ mobilization, whereas these responses to thrombin were within normal ranges. GTPase activity was also decreased when the patient's platelet membrane was challenged with STA2. On the other hand, lysophosphatidylinositol formation, which is a direct indicator of phospholipase A2 (PLA2) activation, was found to be normal when the [3H]-inositol-labeled platelets were challenged with STA2. Thromboxane B2 (TXB2) was also produced in response to STA2. These results suggested that the abnormality in these platelets was impaired coupling between TXA2 receptor and phospholipase C (PLC) activation. Furthermore, it is also suggested that the activation of PLA2 and PLC are separable events in thromboxane-induced platelet activation.

Adult↗